The LIR has previously demonstrated that lymphoid organs are the major reservoir in vivo of human immunodeficiency virus type 1 (HIV-1). The effect of antiretroviral therapy on HIV burden and expression was evaluated by sampling peripheral blood (PB) and lymphoid tissue (LT) of patients at baseline and after 8 weeks of either remaining untreated, remaining on zidovudine (zdv), initiating zdv, or adding didanosine (ddI) to zdv. In individuals who did not undergo a change in therapy, patterns of histopathology, viral trapping, viral burden, and viral replication remained constant between week 0 and week 8. In patients with intermediate-to-late stage HIV disease who added ddI to ongoing zdv therapy, decreases in viral replication in LT were paralleled by decreases in plasma viremia, thus substantiating measurement of plasma viremia as a valid marker in assessing response to antiretroviral therapy. In patients in early stage HIV disease who initiated zdv therapy, no significant changes were observed in any measure of viral load in the peripheral blood and lymph node compartments. The effects of an immunomodulatory agent, dinitrochlorobenzene (DNCB), in combination with Chinese herbs were evaluated by sampling PB and LN at baseline and after 6 months of initiating DNCB and herbs (DNCB plus herbs group) or herbs alone (herbs group). CD4+ T-cell counts remained stable in both groups. Total CD8+ T-cell counts remained unchanged; however, there was a significant increase in the percentage of CD8+CD38+ cells in both groups. Viral burden and viral replication in PB and LN remained stable in both groups. Analysis of cytokine (interferon-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10) expression from PBMC and LNMC revealed a TH-like pattern at baseline which did not change at the 6 month time point in either group.